C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4

被引：0
作者：
Bruno Di Stefano
Samuel Collombet
Janus Schou Jakobsen
Michael Wierer
Jose Luis Sardina
Andreas Lackner
Ralph Stadhouders
Carolina Segura-Morales
Mirko Francesconi
Francesco Limone
Matthias Mann
Bo Porse
Denis Thieffry
Thomas Graf
机构：
[1] Centre for Genomic Regulation (CRG),
[2] The Barcelona Institute of Science and Technology,undefined
[3] Dr. Aiguader 88,undefined
[4] Universitat Pompeu Fabra (UPF),undefined
[5] Institut de Biologie de l’Ecole Normale Supérieure (IBENS),undefined
[6] CNRS UMR8197,undefined
[7] INSERM U1024,undefined
[8] Ecole Normale Supérieure,undefined
[9] PSL Research University,undefined
[10] The Finsen Laboratory,undefined
[11] Rigshospitalet,undefined
[12] Faculty of Health Sciences,undefined
[13] University of Copenhagen,undefined
[14] Biotech Research and Innovation Centre (BRIC),undefined
[15] University of Copenhagen,undefined
[16] Ole Maaløes Vej 5,undefined
[17] Danish Stem Cell Center (DanStem),undefined
[18] Faculty of Health Sciences,undefined
[19] University of Copenhagen,undefined
[20] Max Planck Institute of Biochemistry,undefined
[21] Present addresses: Department of Molecular Biology,undefined
[22] Massachusetts General Hospital and Harvard Medical School,undefined
[23] Boston,undefined
[24] Massachusetts 02114,undefined
[25] USA (B.D.S.); Max F. Perutz Laboratories,undefined
[26] University of Vienna,undefined
[27] Vienna Biocenter (VBC),undefined
[28] Dr. Bohr-Gasse 9/3,undefined
[29] 1030 Vienna,undefined
[30] Austria (A.L.).,undefined
来源：
Nature Cell Biology | 2016年 / 18卷
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摘要：
Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) is typically inefficient and has been explained by elite-cell and stochastic models. We recently reported that B cells exposed to a pulse of C/EBPα (Bα′ cells) behave as elite cells, in that they can be rapidly and efficiently reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPα post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell gene silencing and Brd4 for the activation of the pluripotency program. C/EBPα also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. Bα′ cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBPα.
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页码：371 / 381
页数：10
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